Respiratory syncytial virus (RSV) is a major cause of lower respiratory infections in infants and the elderly. Bronchiolitis and pneumonia caused by RSV are the primary reasons for hospitalization of young children. While the primary infection is the most serious, and the presence of neutralizing antibody will protect against pulmonary infection, re-infection of the upper airway throughout life is the rule. Although relatively little is known about RSV infection of the upper respiratory tract, recent literature supports the idea that RSV may be the predominant viral pathogen in terms of predisposition to bacterial otitis media. Currently no RSV vaccine is available. Progress in RSV vaccine development has been hampered by the problems inherent in vaccinating newborns (before the peak of primary infection at 2 to 4 months), as well as the legacy of vaccine-enhanced illness during trials of a formalinized whole virus vaccine in the 1960s. We have developed mouse and chinchilla models of nasopharyngeal and Eustachian tube RSV infection, and developed tools to study them. Using these models we will be able to test the role of RSV in bacterial otitis media (chinchilla), develop vaccine candidates that will provide mucosal and CTL immunity against RSV without causing severe immunopathology (mouse), and test the ability of these candidates to protect against viral and bacterial otitis media (chinchilla). We suggest that a vaccine to prevent upper airway infection by RSV could be used in older infants to prevent otitis media as well as providing some measure of protection against lower airway disease in young children and adults. [unreadable] [unreadable]